crossing96/oncoscreening huggingface dataset:
Cigarette smoking is associated with adverse pathological response and increased disease recurrence amongst patients with muscle-invasive bladder cancer treated with cisplatin-based neoadjuvant chemotherapy and radical cystectomy: a single-centre experience.	OBJECTIVE: To investigate the association between smoking status and pathological response to cisplatin-based neoadjuvant chemotherapy (NAC) and survival outcomes in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy (RC). PATIENTS AND METHODS: We reviewed 201 patients treated with NAC and RC for cT2-cT4N0M0 BC between 01/1999 and 01/2015. Smoking status was categorised as: 'never', 'former', and 'current' smoker. Pathological response to NAC was defined as: complete (ypT0N0), partial (ypTis/Ta/T1, N0), and no response (ypT2-4 or ypN+). Clinicopathological characteristics were analysed according to smoking status. Logistic regression analyses tested the association between smoking status and pathological response to NAC. Cox regression analyses tested risk factors associated with recurrence, overall (OM) and cancer-specific mortality (CSM). RESULTS: Overall, there were 58 (28.9%) never smokers, 87 (43.3%) former smokers, and 56 (27.9%) current smokers. No response to NAC was more frequently noted in current smokers (73.2%; P = 0.007). Former smoker (odds ratio [OR] 2.28; P = 0.024) and current smoker statuses (OR 4.52; P < 0.001) were significantly associated with no response to NAC, after adjusting for age, gender, Charlson Comorbidity Index, and clinical stage. Similarly, current smoking status (hazard ratio [HR] 2.14; P = 0.03) and extravesical pathological tumour stage (HR 3.31; P < 0.001) were independently associated with an increased risk of recurrence after RC. CONCLUSION: Cigarette smoking was significantly associated with adverse pathological response to cisplatin-based NAC in patients with MIBC treated with RC. Current smokers were at significantly higher risk of disease recurrence as compared to former and never smokers.	bladder
Impact of adjuvant chemotherapy in patients with adverse features and variant histology at radical cystectomy for muscle-invasive carcinoma of the bladder: Does histologic subtype matter?	BACKGROUND: The use of adjuvant chemotherapy (AC) in pure urothelial carcinoma of the bladder is established. Regarding variant histology, there is a gap in knowledge concerning the optimal treatment after radical cystectomy (RC). The objective of this study was to assess the effect of AC on overall survival (OS) in patients who had pure urothelial carcinoma, urothelial carcinoma with concomitant variant histology, or another pure variant histology. METHODS: Within the National Cancer Data Base, 15,397 patients who underwent RC for nonmetastatic, localized carcinoma of the bladder and had positive lymph nodes (T2N+) or locally advanced stage (≥T3N0/N+) were identified, excluding those who had previously received neoadjuvant chemotherapy. Multivariable Cox regression models were used to examine the specific effect of AC on OS stratified by each distinct histologic subtype, including pure urothelial carcinoma, micropapillary or sarcomatoid differentiation, squamous cell carcinoma, adenocarcinoma, and neuroendocrine tumors. To account for immortal time bias, Cox regression analyses and Kaplan-Meier analyses were conducted with a landmark at 3 months. RESULTS: In multivariable landmark analyses, AC compared with initial observation was associated with an OS benefit for patients who had pure urothelial carcinoma (hazard ratio, 0.87; 95% confidence interval, 0.82-0.91), whereas no differences were observed with regard to those who had variant histology. CONCLUSIONS: Multivariable Cox regression landmark analysis revealed a survival benefit from AC for patients with a pure urothelial carcinoma. However, a survival benefit of AC for patients who had urothelial carcinoma with concomitant variant histology or other pure variant histology was not demonstrated.	bladder
Identification of several cell cycle relevant genes highly correlated with the progression and prognosis of human bladder urothelial tumor.	The incidence of bladder cancer (BCa) in China is the highest among genitourinary system tumors, and its progression is affected by multitudinous pathways, of which cell cycle progress plays an important role. This study screened and enriched differentially expressed genes (DEGs) from four gene expression profiles using bioinformatics analysis methods. The enrichment and analysis of gene function showed that these genes were highly correlated with cell cycle regulation. Identification of candidate small molecules was conducted to evaluate the application of clinical transformation in these DEGs. Prognostic and stage-related expression analysis further sorted five highly expressed genes associated with worse prognosis and higher stages in patients with BCa. Further analysis revealed their interaction in cell cycle regulation and genetical alteration. Meanwhile, we validated the elevated expression of these genes through transcription and translation levels. Taking the results together, we could infer that these five genes are valuable in diagnosis, prediction, and providing candidate therapeutic targets for patients with BCa in different stages.	bladder
[Systemic treatment of metastatic tumors of the upper urinary tract].	BACKGROUND: Similar to bladder cancer, more than 95% tumors of the upper urinary tract are urothelial carcinoma. At initial diagnosis approximately 60% of the tumors are already invasive. In case of distant metastasis (M+) there is no benefit of radical nephroureterectomy. In those cases, systemic therapy is indicated. OBJECTIVES: The aim of this article is to present a systematic overview of different therapies in patients with metastatic upper tract urothelial carcinoma (UTUC). RESULTS: Currently there are insufficient data upon which the recommendations for treatment of locally advanced and metastatic UTUC can be based. Cisplatin-based chemotherapy is the gold standard in first-line treatment of metastatic UTUC. Due to a lower toxicity compared to MVAC (methotrexate, vinblastine, adriamycin plus cisplatin), gemcitabine and cisplatin have become standard. However, carboplatin-based chemotherapies should not be considered interchangeable. Immunomodulatory therapies using checkpoint inhibition, particularly with antibodies directed against PD-1 (programmed cell death 1), PD-L1 (programmed cell death ligand 1) or CTLA-4 (cytotoxic T‑lymphocyte antigen-4) have shown significant antitumor activity with tolerable safety profiles and durable responses in patients with locally advanced and metastatic urothelial carcinoma. In those patients, unfit for cisplatin-based chemotherapy, good response rates have been reported in case of a positive PD-L1 status. However, preliminary data of the KEYNOTE-361 and IMvigor130 studies showed a reduced survival in case of low PD-L1 expression.	bladder
Facial Palsy Induced by Checkpoint Blockade: A Single Center Retrospective Study.	The augmented immune response caused by immune checkpoint inhibitors leads to the emergence of a class of side effects called immune-related adverse events (irAEs). Facial palsy (FP) is rarely reported as an irAE. In this retrospective study, we reviewed the records of 353 patients treated with immunotherapy in our center from 2015-2018. We identified 4 male patients and 1 female patient with FP. Four had metastatic melanoma and were treated with ipilimumab either as monotherapy or in combination with nivolumab or pembrolizumab. The remaining patient had metastatic bladder cancer, treated with atezolizumab. FP was unilateral and occurred 1-23 weeks after starting immunotherapy. FP was part of a more diffuse neuropathic process in 3 of our patients. Lymphocytic pleocytosis was seen in the cerebrospinal fluid of 3 patients who had lumbar punctures. Magnetic resonance imaging showed enhancement of the intracranial portion of the affected facial nerve in 4 patients. The outcome was favorable in all of the patients noting that 1 patient had incomplete recovery. We conclude that FP, in isolation or as a part of a polyneuropathy, is common among neurological irAEs associated with checkpoint inhibitors and generally has a good prognosis.	bladder
MicroRNA-124-3p suppresses cell migration and invasion by targeting ITGA3 signaling in bladder cancer.	BACKGROUND: A growing body of studies have demonstrated the aberrant expression of microRNAs (miRNAs) contributes to human tumor metastasis. MicroRNA-124-3p (miR-124-3p), which is down-regulated in various cancers, has been found to be involved in several signaling pathways relevant to tumor cell migration and invasion. However, the roles of miR-124-3p in human bladder cancer remain unclear. This study aims to investigate the functional significance of miR-124-3p and to understand how it targets the integrin receptor, and thus affects the progression of human bladder cancer. METHODS: Clinical specimens from 36 patients and three human bladder cancer cell lines were analyzed for miR-124-3p and integrin α3 (ITGA3) . To investigate the effects of miR-124-3p and ITGA3 on proliferation of bladder cancer cells, the MTT assay, colon-formation assay and flow cytometry were performed. In addition, wound healing assay and transwell assay were carried out to examine the migration and invasion of the bladder cancer cells transfected with miR-124-3p mimics or si-ITGA3. The luciferase reporter assay, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were applied to validate the miR-124-3p directly binding with ITGA3. Finally, western blot was used to examine the expression level of the proteins involved in FAK/PI3K/AKT and FAK/Src signal pathway as well as epithelial-mesenchymal transition (EMT) process. RESULTS: The down-regulation of miR-124-3p and up-regulation of ITGA3 were observed in clinical specimens and bladder cancer cell lines. Overexpression of miR-124-3p or silencing ITGA3 inhibited tumor cell migration and invasion. Luciferase assay confirmed miR-124-3p directly targets ITGA3, and western blot suggested that miR-124-3p plays a crucial role in the EMT and metastasis of human bladder cancer through FAK/PI3K/AKT and FAK/Src signaling mechanism. Also, by targeting ITGA3, miR-124-3p can modulate the expression of N- and E-cadherin, and thus inhibit the EMT. CONCLUSIONS: By targeting ITGA3 and downstream FAK/PI3K/AKT and FAK/Src signaling pathways, miR-124-3p suppresses cell migration and invasion in bladder cancer. Our study reasonably speculates that miR-124-3p can be potentially developed as a therapeutic target and prognostic biomarker for bladder cancer.	bladder
Impact of endothelial nitric oxide synthase polymorphisms on urothelial cell carcinoma development.	"OBJECTIVES: Urothelial cell carcinoma (UCC), a major malignancy of the genitourinary tract, is induced through carcinogenic etiological factors. Endothelial nitric oxide synthase (eNOS) is one of the major isoforms of nitric oxide synthase and is involved in various pathophysiologic and physiologic processes. In this study, eNOS single-nucleotide polymorphisms were investigated to evaluate UCC susceptibility and clinicopathological characteristics. MATERIALS AND METHODS: Two single-nucleotide polymorphisms of eNOS in 431 patients with UCC and 862 controls without cancer were analyzed using real-time polymerase chain reaction. RESULTS: The results showed that 272 men with UCC having eNOS 894 G > T rs1799983 ""GT + TT"" variants had a high risk of developing a large tumor (T1-T4, P = 0.038). Furthermore, a correlation was observed between the expressions of eNOS and invasive tumor, metastasis and poor survival in urothelial carcinoma in The Cancer Genome Atlas data set. CONCLUSION: Our results indicated that male patients with UCC carrying eNOS 894 G > T rs1799983 ""GT + TT"" genetic variants have a high risk of developing a large tumor, and eNOS polymorphisms may serve as a marker or therapeutic target in UCC treatment."	bladder
Highly sensitive ratiometric fluorescent paper sensor for the urine assay of cancer.	Telomerase, as a valuable biomarker, is an important target in cancer diagnosis. Here, we report a ratiometric fluorescent probe for telomerase activity assay in urine and bladder cancer diagnoses based on the color change of Rox-DNA functionalized quantum dots (QDs). The green fluorescence of the QDs was sensitive to H(2)O(2), but the red fluorescence of Rox showed no change. An HRP-mimicking hemin/G-quadruplex, which was formed with the help of telomerase activity, catalyzed H(2)O(2) into H(2)O and O(2). This quadruplex effectively avoided H(2)O(2) interference with green fluorescence. In the presence of H(2)O(2), the detected color changed from red to yellow-green by increasing the telomerase concentration. The detection limit (LOD) was 10 cells, and response time was within 60 min. More importantly, a paper sensor was developed based on this probe and used for the assay of telomerase activity in urine samples. The results were highly sensitive and reproducible, and visual semi-quantitative detection was realized using the naked eye.	bladder
Handling and reporting of pelvic lymphadenectomy specimens in prostate and bladder cancer: a web-based survey by the European Network of Uropathology.	AIMS: Pathological evaluation of lymphadenectomy specimens plays a pivotal role in accurate lymph node (LN) staging. Guidelines standardising the gross handling and reporting of pelvic LN dissection (PLND) in prostate (PCa) and bladder (BCa) cancer are currently lacking. This study aimed to establish current practice patterns of PLND evaluation among pathologists. METHODS AND RESULTS: A web-based survey was circulated to all members of the European Network of Uropathology (ENUP), comprising 29 questions focusing on the macroscopic handling, LN enumeration and reporting of PLND in PCa and BCa. Two hundred and eighty responses were received from pathologists throughout 23 countries. Only LNs palpable at grossing were submitted by 58%, while 39% routinely embedded the entire specimen. Average LN yield from PLND was ≥10 LNs in 56% and <10 LNs in 44%. Serial section(s) and immunohistochemistry were routinely performed on LN blocks by 42% and <1% of respondents, respectively. To designate a LN microscopically, 91% required a capsule/subcapsular sinus. In pN+ cases, 72% reported the size of the largest metastatic deposit and 94% reported extranodal extension. Isolated tumour cells were interpreted as pN1 by 77%. Deposits identified in fat without associated lymphoid tissue were reported as tumour deposits (pN0) by 36% and replaced LNs (pN+) by 27%. LNs identified in periprostatic fat were included in the PLND LN count by 69%. CONCLUSION: This study highlights variations in practice with respect to the gross sampling and microscopic evaluation of PLND in urological malignancies. A consensus protocol may provide a framework for more consistent and standardised reporting of PLND specimens.	bladder
A three-gene methylation marker panel for the nodal metastatic risk assessment of muscle-invasive bladder cancer.	PURPOSE: In this study, we aimed to identify a DNA methylation pattern suitable for prognosis assessment of muscle-invasive bladder cancer and to investigate metastasis-associated processes regulated by DNA methylation. METHODS: Genome-wide methylation analysis was performed on 23 muscle-invasive bladder tumors by microarray analysis. Validation was performed by the qAMP technique in two different patient cohorts (n = 32 and n = 100). mRNA expression was analyzed in 12 samples. Protein expression was determined using tissue microarrays of 291 patients. Bladder cancer cell lines T24 and 253JB-V were used for functional analyses. RESULTS: Microarray analyses revealed KISS1R, SEPT9 and CSAD as putative biomarkers with hypermethylation in node-positive tumors. The combination of the three genes predicted the metastatic risk with sensitivity of 73% and specificity of 71% in cohort 1, and sensitivity of 82% and specificity of 54% in cohort 2. mRNA expression differences were detected for KISS1R (p = 0.04). Protein expression of KISS1R was significantly reduced (p < 0.001). Knockdown of SEPT9v3 resulted in increased cell migration by 28% (p = 0.04) and increased invasion by 22% (p = 0.004). KISS1R overexpression resulted in decreased cell migration (25%, p = 0.1). CONCLUSIONS: We identified a methylation marker panel suitable to differentiate between patients with positive and negative lymph nodes at time of cystectomy. This enables a risk assessment for patients who potentially benefit from extended lymph node resection as well as from neoadjuvant chemotherapy and could improve the survival rates. Furthermore, we examined the impact of putative markers on tumor behavior. Hence, KISS1R and SEPT9 could represent a starting point for the development of novel therapy approaches.	bladder
Exercise Training Impacts Cardiac Mitochondrial Proteome Remodeling in Murine Urothelial Carcinoma.	"Cardiac dysfunction secondary to cancer may exert a negative impact in patients' tolerance to therapeutics, quality of life, and survival. The aim of this study was to evaluate the potential therapeutic effect of exercise training on the heart in the setting of cancer, after diagnosis. Thus, the molecular pathways harbored in heart mitochondria from a murine model of chemically-induced urothelial carcinoma submitted to 8-weeks of high intensity treadmill exercise were characterized using mass spectrometry-based proteomics. Data highlight the protective effects of high intensity exercise training in preventing left ventricle diastolic dysfunction, fibrosis, and structural derangement observed in tumor-bearing mice. At the mitochondrial level, exercise training counteracted the lower ability to produce ATP observed in the heart of animals with urothelial carcinoma and induced the up-regulation of fatty acid oxidation and down-regulation of the biological process ""cardiac morphogenesis"". Taken together, our data support the prescription of exercise training after cancer diagnosis for the management of disease-related cardiac dysfunction."	bladder
Large-scale profiling of serum metabolites in African American and European American patients with bladder cancer reveals metabolic pathways associated with patient survival.	BACKGROUND: African Americans (AAs) experience a disproportionally high rate of bladder cancer (BLCA) deaths even though their incidence rates are lower than those of other patient groups. Using a metabolomics approach, this study investigated how AA BLCA may differ molecularly from European Americans (EAs) BLCA, and it examined serum samples from patients with BLCA with the aim of identifying druggable metabolic pathways in AA patients. METHODS: Targeted metabolomics was applied to measure more than 300 metabolites in serum samples from 2 independent cohorts of EA and AA patients with BLCA and healthy EA and AA controls via liquid chromatography-mass spectrometry, and this was followed by the identification of altered metabolic pathways with a focus on AA BLCA. A subset of the differential metabolites was validated via absolute quantification with the Biocrates AbsoluteIDQ p180 kit. The clinical significance of the findings was further examined in The Cancer Genomic Atlas BLCA data set. RESULTS: Fifty-three metabolites, mainly related to amino acid, lipid, and nucleotide metabolism, were identified that showed significant differences in abundance between AA and EA BLCA. For example, the levels of taurine, glutamine, glutamate, aspartate, and serine were elevated in serum samples from AA patients versus EA patients. By mapping these metabolites to genes, this study identified significant relations with regulators of metabolism such as malic enzyme 3, prolyl 3-hydroxylase 2, and lysine demethylase 2A that predicted patient survival exclusively in AA patients with BLCA. CONCLUSIONS: This metabolic profile of serum samples might be used to assess risk progression in AA BLCA. These first-in-field findings describe metabolic alterations in AA BLCA and emphasize a potential biological basis for BLCA health disparities.	bladder
Bladder cancer extracellular vesicles drive tumorigenesis by inducing the unfolded protein response in endoplasmic reticulum of nonmalignant cells.	The field cancerization effect has been proposed to explain bladder cancer's multifocal and recurrent nature, yet the mechanisms of this effect remain unknown. In this work, using cell biology, flow cytometry, and qPCR analyses, along with a xenograft mouse tumor model, we show that chronic exposure to tumor-derived extracellular vesicles (TEVs) results in the neoplastic transformation of nonmalignant human SV-HUC urothelial cells. Inhibition of EV uptake prevented this transformation. Transformed cells not only possessed several oncogenic properties, such as increased genome instability, loss of cell-cell contact inhibition, and invasiveness, but also displayed altered morphology and cell structures, such as an enlarged cytoplasm with disrupted endoplasmic reticulum (ER) alignment and the accumulation of smaller mitochondria. Exposure of SV-HUC cells to TEVs provoked the unfolded protein response in the endoplasmic reticulum (UPR(ER)). Prolonged induction of UPR(ER) signaling activated the survival branch of the UPR(ER) pathway, in which cells had elevated expression of inositol-requiring enzyme 1 (IRE1), NF-κB, and the inflammatory cytokine leptin, and incurred loss of the pro-apoptotic protein C/EBP homologous protein (CHOP). More importantly, inhibition of ER stress by docosahexaenoic acid prevented TEV-induced transformation. We propose that TEVs promote malignant transformation of predisposed cells by inhibiting pro-apoptotic signals and activating tumor-promoting ER stress-induced unfolded protein response and inflammation. This study provides detailed insight into the mechanisms underlying the bladder cancer field effect and tumor recurrence.	bladder
Urinary Cytokine Profile to Predict Response to Intravesical BCG with or without HS-410 Therapy in Patients with Non-muscle-invasive Bladder Cancer.	BACKGROUND: Despite extensive research to identify biomarkers of response in patients with non-muscle-invasive bladder cancer (NMIBC), there is no biomarker to date that can serve this purpose. Herein, we report how we leveraged serial urine samples to query a panel of cytokines at varying time points in an attempt to identify predictive biomarkers of response in NMIBC. METHODS: Serial urine samples were collected from 50 patients with intermediate- or high-risk NMIBC enrolled in a phase II study, evaluating intravesical BCG ± intradermal HS-410 therapy. Samples were collected at baseline, week 7, week 13, week 28, and at end of treatment. A total of 105 cytokines were analyzed in each sample. To predict outcome of time-to-event (recurrence or progression), univariate and multivariable Cox analyses were performed. RESULTS: Fifteen patients developed recurrence and 4 patients progressed during the follow-up period. Among clinicopathologic variables, ever-smoker versus nonsmoker status was associated with an improved response rate (HR 0.38; 95% confidence interval (CI), 0.14-0.99; P = 0.04). In the most clinically relevant model, the percent change (for 100 units) of IL18-binding protein-a (HR 1.995; 95% CI, 1.16-3.44; P = 0.01), IL23 (HR 1.12; 95% CI, 1.01-1.23; P = 0.03), IL8 (HR 0.27; 95% CI, 0.07-1.08; P = 0.06), and IFNγ-induced protein-10 (HR 0.95; 95% CI, 0.91-0.99; P = 0.04) at week 13 from baseline best predicted time to event. CONCLUSIONS: Urinary cytokines provided additional value to clinicopathologic features to predict response to immune-modulating agents in patients with NMIBC. IMPACT: This study serves as a hypothesis-generating report for future studies to evaluate the role of urine cytokines as a predictive biomarker of response to immune treatments.	bladder